Role of Cytoreductive Nephrectomy in mRCC - Episode 16
Rana R. McKay, MD: There are several other trials that are looking at novel combinations for specific subsets of patients. The CALYPSO data of savolitinib, which is a potent c-Met inhibitor, combined with durvalumab was recently presented in patients with papillary RCC [renal cell carcinoma]. Here, we saw response rates of around 26%.
So it’s exciting to see variations in histology of RCC being represented in clinical trials, because those with non-clear-cell disease are largely unrepresented in most of these studies. Trials were exclusive of patients who had a clear-cell component. I think looking at studies that really highlight the efficacy of these agents in non-clear-cell patients will be important.
A trial of atezolizumab plus cabozantinib will include patients who have papillary and unclassified RCC. There’s also a trial looking at nivolumab-ipilimumab plus cabozantinib. We are looking at that combination in patients with non-clear-cell histology.
Another unmet need is patients who have bone metastases from RCC. We know that those patients have declines in their quality of life and also decreased survival. And so, we’ve designed a specific trial through the Alliance [for Clinical Trials in Oncology] cooperative group, which is now open and is accruing patients for the combination of cabozantinib with or without radium 223 dichloride, which is liquid radiopharmaceutical that specifically targets bone metastases in the bone marrow niche. It will be exciting to see how new drugs with new mechanisms of action work in this patient population.
Additionally, there are some other questions being asked. Does everybody need a frontline combination? We know that based on the toxicity rates, about a third of patients require high-dose steroids to treat immune-related toxicities. Can we adapt our trials to response? If a patient is having a dramatic response to therapy, can we safely stop therapy? Or if patients don’t have a response to checkpoint inhibition monotherapy—nivolumab monotherapy—can we layer in a CTLA4 blockade with ipilimumab?
There are 3 trials that are specifically looking at this exact question—different iterations of adapting checkpoint inhibition therapy. One of the trials was recently presented at ESMO [the European Society for Medical Oncology Congress] last year. It was called the TITAN RCC trial. This trial looked at adding ipilimumab for 2 doses when patients did not have an objective response to nivolumab alone. And then, if there was a resistant PD [progressive disease] or SD [stable disease], an additional 2 doses were added. It’s hard to interpret some of the trials because they included a very heterogeneous patient population—both patients treated in the frontline as well as the second line. But it seems that the delta from the TITAN trial that was presented was about 10%. The added rescue was probably about 10% with the addition of ipilimumab patients who were nonresponders to nivolumab.
We’re awaiting the data from OMNIVORE, which is a multicenter study run through the Dana-Farber Cancer Institute. This trial is looking at answering the question of whether following induction with nivolumab alone, based on response, can you stop the nivolumab treatment in those patients who have a confirmed CR [complete response] or PR [partial response]? Or if they did not have a response, actually adding in 2 doses of ipilimumab. There’s also another study looking at the role of salvage ipilimumab.
I think all these interesting studies may further enhance the field and answer some unmet questions that are out there.
Ulka Vaishampayan, MD: I agree, Rana. That was a wonderful summary. Also, let’s not forget that non-clear-cell histology in kidney cancer remains a huge unmet need. There is the SWOG S1500 PAPMET trial comparing sunitinib to cabozantinib. The trial has completed accrual, and results are awaited. There were 2 other arms in the study—savolitinib, a c-Met inhibitor, as well as crizotinib. Both of these arms were stopped because of futility analysis. And now the study will finally report out results of sunitinib in comparison with cabozantinib. The hope with those results is that it will establish a baseline for future comparison and will establish a standard frontline therapy for papillary metastatic kidney cancer.
There are other non-clear-cell histology studies. Of course, there are studies of axitinib and nivolumab ongoing in the translocation type of kidney cancer. There is a study by the cooperative group with that combination. And there are more and more studies that are needed to look at these small incidences of non-clear-cell histology.
The other study that is noteworthy is a combination of atezolizumab and bevacizumab after previous therapy in non-clear-cell histology. That showed fairly promising results. This study was led by Dana-Farber. Rana, of course, is 1 of the lead authors on that. Any other comments?
Mehmet Asim Bilen, MD: Ulka, I want to highlight the ICONIC trial, which is run by Andrea Apolo from the NCI [National Cancer Institute]. She did great work in terms of combining nivolumab-cabozantinib and also combining nivolumab-ipilimumab-cabozantinib for a rarer GU [genitourinary] tumor type. Among this rare GU tumor type, a number of rare RCC patients can go on the trial. One of them is renal medullary carcinoma. This is a challenging subgroup, and they still need to come up with a good therapy option for those patients. Again, rare collecting duct and papillary subtypes can also enroll in the ICONIC trial, which has seen the triplet in those rare populations.
Ulka Vaishampayan, MD: I agree. That is an ongoing trial, and it needs to be supported.
Matthew T. Campbell, MD, MS: Real quick, I want to mention that there are several other studies for patients who have non-clear-cell histologies. We have a CABOSUN study that is similar to PAPMET, in terms of looking at sunitinib versus cabozantinib in the frontline setting. We’re including patients who have additional histologies as opposed to just papillary. And so we’re accruing patients with chromophobe unclassified RCC. The only exclusions are for patients with renal medullary cancer or collecting duct.
And a quick plug, again, for renal medullary cancer: This is a huge passion for my colleagues, Dr Nizar Tannir and Pavlos Msaouel. We have a number of clinical trials for these patients, so I think it would be fantastic if we were able to continue to identify and treat these patients with this very aggressive disease.
My final plug, and this is about cost, because I think this is really crucial as we’ve talked about all these therapies: As it stands right now, it’s important for everyone to know that immune checkpoint therapy is currently covered under Medicare Part B. There has been some talk about moving it to Medicare Part D, which I think would be really threatening to patients. In Medicare Part D, many patients are on the hook for 20% co-pays. And so I think it’s imperative that we ask Congress to look at the ability for Medicare patients to accept co-pay programs, which they’re currently not allowed to use, and to also consider negotiation of cost with companies.
Ulka Vaishampayan, MD: OK, with that we will wrap up our Peer Exchange® discussion. Thank you, everyone, for a very stimulating and exciting discussion. Good evening.
Mehmet Asim Bilen, MD: Thank you.
Transcript Edited for Clarity